Uncouplers of Oxidative Phosphorylation In normal mitochondria the rate of electron transfer is tightly coupled to...

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Uncouplers of Oxidative Phosphorylation In normal mitochondria the rate of electron transfer is tightly coupled to the demand for ATP. When the rate of use of ATP is relatively low, the rate of electron transfer is low; when demand for ATP increases, electron-transfer rate increases. Under these conditions of tight coupling, the number of ATP molecules produced per atom of oxygen consumed when NADH is the electron donor-the P/O ratio-is about 2.5. (a) Predict the effect of a relatively low and a relatively high concentration of uncoupling agent on the rate of electron transfer and the P/O ratio. (b) Ingestion of uncouplers causes profuse sweating and an increase in body temperature. Explain this phenomenon in molecular terms. What happens to the P/O ratio in the presence of uncou- plers? (e) The uncoupler 2,4-dinitrophenol was once prescribed as a weight-reducing drug. How could this agent, in principle, serve as a weight-reducing aid? Uncoupling agents are no longer prescribed because some deaths occurred following their use. Why might the ingestion of uncouplers lead to death? Uncouplers of Oxidative Phosphorylation In normal mitochondria the rate of electron transfer is tightly coupled to the demand for ATP. When the rate of use of ATP is relatively low, the rate of electron transfer is low; when demand for ATP increases, electron-transfer rate increases. Under these conditions of tight coupling, the number of ATP molecules produced per atom of oxygen consumed when NADH is the electron donor-the P/O ratio-is about 2.5. (a) Predict the effect of a relatively low and a relatively high concentration of uncoupling agent on the rate of electron transfer and the P/O ratio. (b) Ingestion of uncouplers causes profuse sweating and an increase in body temperature. Explain this phenomenon in molecular terms. What happens to the P/O ratio in the presence of uncou- plers? (e) The uncoupler 2,4-dinitrophenol was once prescribed as a weight-reducing drug. How could this agent, in principle, serve as a weight-reducing aid? Uncoupling agents are no longer prescribed because some deaths occurred following their use. Why might the ingestion of uncouplers lead to death?

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